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Abstract: 1-Methyl, 4-phenyl, 1,2,3,6-tetrahydropiridine (MPTP) is a neurotoxin, widely used to produce experimental models of Parkinson Disease in rodents and primates. Although dopaminergic neurons are the most sensitive to MPTP neurotoxicity, different neuronal subtypes are affected. Among these, recent studies indicate that MPTP may produce pathological effects on spinal neurons. In fact, MPTP activates apoptotic proteins within the spinal cord and in particular within the motor neurons, suggesting commonalities between Parkinson Disease and Amyotrophic Lateral Sclerosis. In order to assess this point, in the present study we measured whether MPTP produces motor neurons loss. We chose a dose of MPTP (20mg/kg×3, 2h apart), which in C57BL/6N mice was able to induce a massive nigrostriatal damage. Since both Parkinson Disease and Amyotrophic Lateral Sclerosis are characterized by altered alpha-synuclein immunostaining, this protein was also evaluated within spinal motor neurons, following MPTP administration. Three different monoclonal antibodies, recognizing distinct epitopes in the sequence of alpha-synuclein were used. Severe dopaminergic cell loss was quantified by stereology within the substantia nigra pars compacta, along with marked decrease of striatal tyrosine hydroxylase densitometry. The same doses of MPTP also caused a significant motor neuron loss in the spinal cord (roughly 30%). Spared motor neurons appeared often dysmorphic and vacuolated and possessed altered alpha-synuclein immunostaining. This latter finding extended to other cell types of the spinal cord. These data indicate that MPTP, apart from being a dopaminergic neurotoxin, produces also motor neuron death, thus bridging experimental Parkinsonism and motor neuron disease. [Copyright &y& Elsevier]

Abstract: The involvement of the spinal cord in parkinsonism is becoming more and more evident based on human autopsies and on experimental models, obtained using specific neurotoxins or genetic manipulations. Besides Parkinson disease, other degenerative disorders characterized by parkinsonism, involve the spinal cord, and multiple neurotransmitters, apart dopamine, are altered in parkinsonism, also in their spinal projections. In the present review we discuss spinal cord pathology of different genetic or toxic experimental models of parkinsonism, as well as the neuropathological reports from autoptic cases of sporadic Parkinson disease and of other neurodegenerative conditions, overlapping with parkinsonism. Furthermore, anatomical distribution of alpha-synuclein in the spinal cord and coeruleo-spinal projections are reviewed, at the light of their possible involvement in spinal neurons degeneration. All these evidences call for an anatomical stemmed novel approach to understand specific features of parkinsonism, which might be due to such an involvement of the spinal cord. Moreover they suggest a common neurodegenerative process, underlying distinct neurodegenerative disorders, to which spinal neurons could be the more sensible. [Copyright &y& Elsevier]